Manufacture of alginic material

ABSTRACT

Partially soluble alginic material in the form of gauze or wool, suitable for the preparation of surgical dressings, based on alginic acid and containing calcium, sodium and acid forms e.g. in the ratio 4 : 5 : 1 and characterised by a calcium content of 2 to 6 percent and a reaction pH of 4 to 7 and a method of manufacture by treatment of the insoluble calcium form of the material with a predetermined quantity of acid and, thereafter, alcoholic alkali.

United States Patent [191 Franklin et al.

[ 11 3,824,997 [451 July 23, 1974 MANUFACTURE OF ALGINIC MATERIAL IInventors: Kenneth John Franklin, Harrow;

Keith Bates, Pinner, both of England Medical Alginates Limited,Perivale, Middlesex, England Filed: Nov. 29, 1971 Appl. No.: 203,039

Assignee:

Foreign Application Priority Data Aug. 12,1971 Great Britain 38010/71References Cited UNITED STATES PATENTS l/l968 Szczesniak 260/20963,653,383 4/1972 Wise, .j. 128/296 FORElGN PATENTS OR APPLICATIONS765,457 l/l957 Great Britain 128/285 Primary Examiner-Lucie H.Laudenslager [57] ABSTRACT Partially soluble alginic material in theform of gauze or wool, suitable for the preparation of surgicaldressings, based on alginic acid and containing calcium, sodium and acidforms e.g. in the ratio 4 5 l and characterised by a calcium content of2 to 6 percent and a reaction pH of 4 to 7 and a method of manufactureby treatment of the insoluble calcium form of the material with apredetermined quantity of acid and, thereafter, alcoholic alkali.

3 Claims, No Drawings MANUFACTURE OF ALGINIC MATERIAL FIELD OF THEINVENTION The present invention relates to alginic material moreparticularly in the form of gauze or wool suitable for the preparationof surgical dressings and to a method for its preparation.

DESCRIPTION OF THE PRIOR ART The use of calcium and sodium alginatematerials made up into wool, gauze and the like in surgery and in thedressing of wounds is now well known. Its use was first described indetail by George Blaine in Annals of Surgery of January 1947. Methods ofpreparation have been described in British Patent Nos. 653,341 and Alginis a material obtained from seaweed. It can be converted into an acidform known as alginic acid which is insoluble and salts of alginic acidcan be obtained some of which'are soluble and some insoluble in waterand body fluids. Thus calcium alginate is insoluble where sodiumalginate is soluble so that by spinning a solution of sodium alginateinto a calcium containing medium, fibres of calcium alginate can beobtained which may be woven or knitted into fabric or gauze. Calciumalginate gauze is not readily soluble in body tissues and to provide amaterial having optimum properties for use in surgery and in thedressing of wounds it is necessary to bring the calcium content of thegauze down to an amount generally about 4 percent or within the range 3to 5 percent by weight, replacing at least part of the calcium by asoluble cation of which sodium is the most common. However usefulproducts can have 2.6 percent Ca.

British Patent Specification 653,341 describes essentially two relatedmethods for producing alginic gauze having the necessary propertiesdescribed above. In the first modification calcium alginate gauzev isleached with acid such as hydrochloric or acetic acid until it is freefrom calcium ions. It is then immersed in an aqueous alcoholic solutionof calcium acetate or calcium chloride containing a known weight ofcalcium ions and this alcoholic solution is then titrated to neutrality(pH 7) with'an alkali such as sodium hydroxide using an appropriateindicator and drained and dried.

In the modification of the process described in British Patent No.653,341 the calcium alginate wool or gauze is immersed in dilutehydrochloric oracetic acid solution such that the amount of acid is notsufficient to leach out more than a predetermined percentage of thecalcium. The material is then washed free from calcium chloride oracetate and finished by titration as above described.

Due to the amount of time taken in bringing the heterogeneous of gauzeand solution into equilibrium, a titration technique is very timeconsuming and for this reason efforts have been made to improve upon theprocess.

In British Patent specification No. 1,231,506 a modified process isdescribed in which the'first step of acid replacement is the same butthe titration step is replaced by the addition to the alcohol vehiclecontaining the gauze of an excess of sodium hydroxide or other alkaliover the calculated stoichiometric quantity of alkali equivalent to theacid used. Excess sodium hydroxide is washed away with more alcoholcontaining some weak acid. The product obtained by the process describedin British Patent specification No. 1,231,506 essentially contains nohydrogen ions on the alginate matrix and will, therefore react with a pHin excess of 7.

THE PROBLEM If all of the calcium removed to bring the content to therange 2 to 6 percent is replaced by sodium, the resultant product willhave a slightly alkaline reaction in contact with water. We have foundthat gauzes providing an alkaline reaction are more subject todiscolouration upon sterilization. This is a problem to whichalginicgauzes are particularly prone and which can be a seriouscommercial disadvantage. We have found that the optimum reaction pH forthe alginic gauze i.e. the pH obtained when the gauze is immersed inwater is within the range 5 to 6, but gauzes and other alginic productswithin the scope of the invention may have a pH within the range 4 to 7.

In order to produce an alginic product reacting with a pH within therange 4 to 7 and having the necessary properties of haemostasis anddispersion with the body and gelling in contact with the wound, thealginate matrix must contain calcium ions (or equivalent insolublecations) sodium ions (or equivalent soluble cations) and hydrogen ionsin a balanced proportion.

THE INVENTION Therefore according to one aspect of our invention weprovide, as a product of manufacture, a partially soluble alginicmaterial in the form of gauze or wool suitable for thepreparation ofsurgical dressings characterised by a reaction pH of 4 to 7 and acalcium content of 2 to 6 percent (preferably 3 to 5 percent) by weight.

Our invention includes a surgical dressing comprising a product asdefined above, in sterile form.

The present invention is also directed at the problem of devising aneconomic process for producing an alginic product suitable for thepreparation of surgical dressings and reacting at a pH within the rangeof 4 to 7, preferably 5 to 6.

In the process of the present invention the calcium alginate rawmaterial is submitted to acid treatment, e.g. as previously proposed, toremove the desired quantity of calcium so as to leave a product having acalcium content of 2 to 6 percent by weight. After washing and removalof excess liquid as necessary or desired, the product is immersed in orotherwise treated with an alcoholic solution of an alkali. In thepreferred process the quantity of alkali is that found by trial anderror to neutralise sufficient of the free alginic acid to cause theresulting product to react at a pH within the desired range i.e. 4 to 7,or preferably 5 to 6, or at least approximately within this range. Thisweight of alkali will not be the stoichiometric weight calculated toreplace all of the hydrogen ion from the matrix but a lower amount.After any necessary agitation, a measure is obtained of the reaction pHof the product. We have found that it is convenient to test the pH ofthe mother liquor for this purpose. The pH of the mother liquor can thenbe adjusted by the addition of acid'or alkali as necessary to bring it,and consequently the reaction pH of the gauze or wool within the desiredrange. The pH of the gauze is preferably checked when the mother liquorhas the desired pI-I, eg by extracting a sample, rinsing briefly inalcohol and immersing it in water containing an indicator or pH meter.The mother liquor is then removed and the final wash is preferably thenmade with a fresh neutral alcoholic solution.

It is however novel and within the broad compass of the invention to addmore than the quantity of alkali calculated to produce a pH reaction inthe gauze of 4 to 7. Adjustment is then made by adding incrementalquantities of acid to the alcoholic solution to bring the pH within thedesired range. If a test of the material shows addition of alkali inexcess of the preferred quantity, the mother liquor can be removed andthe product washed and agitated with a solution of a weak acid e.g. withacetic acid until the pH of a test portion is brought to the desiredrange. In this case further washing with unacidified alcoholic solutionis not necessary although it may be carried out if desired. Howeveraddition of acid can normally be avoided and should preferably beavoided as introducing organic contaminants.

Thus the alkali originally added may be determined by calculation orcalibration by trials to bring the mother liquor to the acid end of thedesired range.

It is preferred to use a weak acid such as acetic acid to adjust the pHfor final washing. The preferred acid for the main calcium replacementreaction is hydrochloric although sulphuric or phosphoric may be used.

Another important feature of the invention which may be considered as anindependent aspect of the invention or as a preferred feature, lies inthe washing and bleaching procedure used for the alginate wool or gauzeprior to the conversion process above described. The raw materialnormally obtained from the spinners and knitters is discoloured andfrequently contains considerable oily residues. It is therefore normallynecessary to clean and purify the raw material before conversion. Thisis carried out by washing the raw material in a mixture of detergent andbleach. It is preferred to add some calcium chloride to the wash liquidto prevent premature replacement of some of the calcium by sodium and soupsetting the calculated balance of ions in the final product. For thesame reason it is preferred to use deionized water in the washingliquid. It has been found that when the washing is completed it is verydifficult to rid the matrix of all traces of bleach, normally sodiumhypochlorite. Where the material is to be used in surgery it is mostdesirable to remove all traces of the bleach and it is normallynecessary to carry out prolonged rinsing for this purpose. We have foundthat the last traces of bleach may be readily removed by treatment witha dilute solution of a suitable non-toxic reducing agent preferably aninorganic reducing agent such as sodium thiosulphate. Preferably a .05percent solution of sodium thiosulphate is used and the treatment iscarried out after the final rinse, the product being given a final rinseafterwards.

The following Example illustrates the preferred process of theinvention.

EXAMPLE Cleaning and Purification 4.00 kg calcium alginate staple fibreor knit is weighed into a stainless steelhorizontal drum washing machineand the following ingredients are added:

Neutralisation Process i The detergent solution, sodium hypochlorite andcalcium chloride are dissolved in the deionized water and added to thewashing machine which is turned on. The machine carries out a washingprocedure with agitation for 20 minutes at about C until the calciumalginate is fully bleached. The washing machine is then operated toremove the wash solution. The machine is filled, agitated and drainedthree times each with 100 l. of deionized water. It is then refilledwith 100 l. of deionized water into which is dissolved 50 g. of sodiumthiosulphate. A washing operation. is carried out for five min- I utesand a sample of fibre is tested fora negative starch/iodine reaction. Onobtaining a negative test the solution is drained and the product rinsedfinally with 100 l. of deionized water.

w Calcium Reduction Process The material after centrifugal spinning istransferred to a second stainless steel horizontal drum washing machinein which it is suspended in l. of industrial methylated spirits T.G.).While the product is being agitated slowly, a sufficient amount ofconcen-. trated sodium hydroxide solution is added to bring the pHof theliquor, after establishment of equilibrium, to 5.5 i 0.5. This amountwill be an amount slightly less than the stoichiometric quantity ascalculated for example in the formula given in British Patentspecification No. 1,231,506. The pH of the material is adjusted ifnecessary to 5.5 i 0.5 by adding increments of concentrated sodiumhydroxide solution or of acetic acid.

When the pH is correct the alcoholic solution is removed bycentrifugalspinning and the product is rinsed with 70 l. of 95 percentT.G. industrial methylated spirits. The supernatant liquid is againremoved by centrifugal spinning and the product dried, e.g. in a tumblerdrier.

Ani m portantprefer red feature of the calcium reduction step is in themanner in which the acid is added. In order to obtain a uniform calciumcontent over the whole of the sample, it is necessary for the acid to bethoroughly dispersed. It has been found that to immerse the sample inready-mixed dilute acid does not result in uniform action of the acidover the whole of the sample. Similarly, too rapid an addition of strongacid to the water in which the sample is contained will give rise tonon-uniform action. The machine preferably used has a horizontal drumand the acid, in its described relatively concentrated form, is passedthrough a perforated tube extending along the length of the drum so asto distribute the acid over the horizontal dimension of the machine. Atthe same time the acid is added slowly over a period of time, forexample 10 minutes or more broadly from 5 to 15 minutes.

normally inconvenient to dry and weigh the material after cleaning andpurification, calculations are normally based upon the impure product.This will contain a varying proportion of calcium normally between 7 and8 percent, depending upon the amount of impurity.

For this reason, theoretical calculations of the quantity of acid andalkali to be used are at best imperfect. Fur thermore the theoreticalcalculation which was, for example, provided in British Patentspecification No. 1,231,506, is only an approximation since it assumesan I irreversible reaction.

desired be adjusted in accordance with the calcium content of the rawmaterial and will of course be differ ent for a different weight ofmaterial. The sodium hy- .droxide is for convenience added in the samevolume as the acid and for 4 kilos of calcium alginate raw materialhaving a calcium content of 8 percent by weight, 840 ml. of 27 percentw/v HaOH will normally bring the pH of the material within the correctpH range (840 ml. of B.P. hydrochloric acid having been used in thereduction step). The stoichiometric amount of sodium hydroxideequivalent to the acid would be 840 ml. of about 40 percent w/v NaOH sothat considerably less than this amount is used. However, it must beborne in mind that not all of the acid used actually replaces calciumdue to the back reaction forming part of the equilibrium process andalso due possibly to incomplete reaction under practical conditions. Forthese reasons,

, theoretical calculation of the exact amounts to be used is of limitedvalue and calibration from experimental trials is more satisfactory.Normally the resultant product having a pH of 5.5, as determined byanalysis, will contain calcium alginate, sodium alginate and alginicacid in approximately the ratio 4 5 1.

What we claim is:

As a product of manufacture, an alginic material in the form of gauze orwool suitable for the preparation of surgical dressings having a pH ofabout 4 to slightly less than 7 and a calcium content of 2 to 6 percentby weight, the pH and calcium content being such that said material ispartially soluble.

2. The product of claim 1 having a-reaction pH of 5 to 6 and a calciumcontent of 3 to 5 percent by weight.

3. A surgical dressing including the product of claim 1 in sterile form.

2. The product of claim 1 having a reaction pH of 5 to 6 and a calciumcontent of 3 to 5 percent by weight.
 3. A surgical dressing includingthe product of claim 1 in sterile form.